RECRUITING

Intravenous Ketamine for Treatment-Resistant Depression

Conditions

Depressive Disorder, Treatment-Resistant Treatment Resistant Depression (TRD)Major Depression MDD TRD Treatment-Resistant Depression Treatment-Resistant Major Depression Ketamine Intravenous Ketamine

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to to evaluate the relationships between peak (% change from baseline) central GABA and Glu levels during a 40-min IV ketamine or normal saline infusion utilizing fMRS, and change in peripheral GABA and Glu levels from baseline to 24-hr postinfusion utilizing LCMS, with baseline to 24-hr post-infusion change in depression (MADRS) in 30 TRD adults.

Official Title

Central and Peripheral GABA and Glutamate Modulation With Intravenous Ketamine for Treatment-Resistant Depression (G2K): A Randomized, Double-Blind, Placebo-Controlled Study

Quick Facts

Study Start:2025-02-10

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06668571

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Ability to provide informed consent * Meets diagnostic criteria for major depressive disorder without psychotic features per the SCID DSM-IV-TR * PHQ-9 total score ≥ 15 at screening * Treatment-resistant depression, as defined by failure of at least two previous antidepressant treatments within the current depressive episode. Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, trial of transcranial magnetic stimulation (TMS) or an acute series of at least 6 administrations of electroconvulsive therapy (ECT) * Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria	* Inability to speak English * Inability to provide consent or have a legal guardian * Patients with a BMI \> 40 kg/m2. * Personality disorder being the primary diagnosis * Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or active psychotic symptoms * Active post-traumatic stress disorder symptoms based on clinical assessment * Ongoing prescription of \> 2 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment * Medications known to affect glutamate (i.e., Riluzole, Carbamazepine) or GABA (zaleplon, zolpidem, zopiclone, Valproate, Gabapentin, Pregabalin, tiagabine, and vigabatrin) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug * Monoamine Oxidase Inhibitors (MAOIs) are prohibited two weeks prior to administration of study drug * Opioid antagonists (naltrexone, naloxone, nalmefene, methylnaltrexone, buprenorphine and naloxone combination) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug * CYP3A4 inducers carbamazepine and modafinil are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug. * Currently undergoing TMS, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression * ECT in the past 6 months * Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study * A history of bleeding in the brain * Arteriovenous malformation or a history of aneurysm * Use of methamphetamine, cocaine, or cannabis. Abuse of stimulant (s) within the prior 12 months * Any current substance use disorder (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their substance use is in complete (not partial) and sustained (\> 1 year) remission * History of traumatic brain injury that resulted in loss of consciousness * History of tonic-clonic (grand mal) seizures * Developmental delay, intellectual disability, or intellectual disorder * Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months * Minor or Major Neurocognitive disorder * Received ketamine treatment for depression within the prior 2 months * History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered * History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months * Hepatic insufficiency (2.5 X ULN for AST or ALT) within 1 year of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver * Gastroesophageal reflux disease that is poorly managed * A diagnosis of Complex Regional Pain Syndrome (CRPS) * Pregnancy, or nursing * History of claustrophobia with active symptoms that would interfere with the MRI * Any contraindication to MRI safety questionnaire

Inclusion Criteria

Exclusion Criteria

* Ability to provide informed consent
* Meets diagnostic criteria for major depressive disorder without psychotic features per the SCID DSM-IV-TR
* PHQ-9 total score ≥ 15 at screening
* Treatment-resistant depression, as defined by failure of at least two previous antidepressant treatments within the current depressive episode. Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, trial of transcranial magnetic stimulation (TMS) or an acute series of at least 6 administrations of electroconvulsive therapy (ECT)
* Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria

* Inability to speak English
* Inability to provide consent or have a legal guardian
* Patients with a BMI \> 40 kg/m2.
* Personality disorder being the primary diagnosis
* Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or active psychotic symptoms
* Active post-traumatic stress disorder symptoms based on clinical assessment
* Ongoing prescription of \> 2 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment
* Medications known to affect glutamate (i.e., Riluzole, Carbamazepine) or GABA (zaleplon, zolpidem, zopiclone, Valproate, Gabapentin, Pregabalin, tiagabine, and vigabatrin) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug
* Monoamine Oxidase Inhibitors (MAOIs) are prohibited two weeks prior to administration of study drug
* Opioid antagonists (naltrexone, naloxone, nalmefene, methylnaltrexone, buprenorphine and naloxone combination) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug
* CYP3A4 inducers carbamazepine and modafinil are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug.
* Currently undergoing TMS, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression
* ECT in the past 6 months
* Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study
* A history of bleeding in the brain
* Arteriovenous malformation or a history of aneurysm
* Use of methamphetamine, cocaine, or cannabis. Abuse of stimulant (s) within the prior 12 months
* Any current substance use disorder (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their substance use is in complete (not partial) and sustained (\> 1 year) remission
* History of traumatic brain injury that resulted in loss of consciousness
* History of tonic-clonic (grand mal) seizures
* Developmental delay, intellectual disability, or intellectual disorder
* Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months
* Minor or Major Neurocognitive disorder
* Received ketamine treatment for depression within the prior 2 months
* History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered
* History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months
* Hepatic insufficiency (2.5 X ULN for AST or ALT) within 1 year of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver
* Gastroesophageal reflux disease that is poorly managed
* A diagnosis of Complex Regional Pain Syndrome (CRPS)
* Pregnancy, or nursing
* History of claustrophobia with active symptoms that would interfere with the MRI
* Any contraindication to MRI safety questionnaire

Contacts and Locations

Study Contact

Nicole Reinicke

CONTACT

507-422-1835

reinicke.nicole@mayo.edu

Principal Investigator

Balwinder Singh, M.D., M.S.

PRINCIPAL_INVESTIGATOR

Mayo Clinic

Study Locations (Sites)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

United States

Collaborators and Investigators

Sponsor: Mayo Clinic

Balwinder Singh, M.D., M.S., PRINCIPAL_INVESTIGATOR, Mayo Clinic

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-10

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2025-02-10

Study Completion Date2027-12-31

Terms related to this study

Keywords Provided by Researchers

Major Depression
Depressive Disorder, Treatment-Resistant
MDD
TRD
Treatment-Resistant Depression
Treatment-Resistant Major Depression
Ketamine
Intravenous Ketamine

Additional Relevant MeSH Terms

Depressive Disorder, Treatment-Resistant
Treatment Resistant Depression (TRD)